4-17585003-C-A

Variant names:

• chr4-17585003-C-A
• NM_015907.3:c.571C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015907.3(LAP3):​c.571C>A​(p.Leu191Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: LAP3 NM_015907.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.474

Genes affected

LAP3 (HGNC:18449): (leucine aminopeptidase 3) Predicted to enable peptidase activity. Predicted to be involved in proteolysis. Located in cytosol; midbody; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18860942).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAP3	NM_015907.3	c.571C>A	p.Leu191Met	missense_variant	Exon 6 of 13	ENST00000226299.9	NP_056991.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAP3	ENST00000226299.9	c.571C>A	p.Leu191Met	missense_variant	Exon 6 of 13	1	NM_015907.3	ENSP00000226299.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.571C>A (p.L191M) alteration is located in exon 6 (coding exon 6) of the LAP3 gene. This alteration results from a C to A substitution at nucleotide position 571, causing the leucine (L) at amino acid position 191 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T;T;.;T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.025
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.75	.;T;T;T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.19	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L;L;.;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.61	N;.;.;N
REVEL	Benign	0.050
Sift	Benign	0.052	T;.;.;T
Sift4G	Benign	0.14	T;T;T;T
Polyphen		0.051	B;B;.;.
Vest4		0.26
MutPred		0.49		Loss of glycosylation at K188 (P = 0.0393);Loss of glycosylation at K188 (P = 0.0393);.;.;
MVP		0.68
MPC		0.23
ClinPred		0.24	T
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-17586626;